Lecture 9 - Glycolysis Flashcards
What is a metabolic pathway
A series of steps found in biochemical reactions that help convert molecules or substrates into different, more readily usable materials
What are the 2 types of metabolic pathway
Anabolic and Catabolic
What is an anabolic pathway
Small molecules are assembled into large ones …energy is required
What is a catabolic pathway
Large molecules are broken down into small ones … energy is released
What is glycolysis
Glycolysis is a series of reactions for the breakdown of Glucose (a 6-carbon molecule) into two molecules of pyruvate (a 3-carbon molecule) under aerobic conditions; or lactate under anaerobic conditions along with the production of a small amount of energy
What are aerobic conditions in the human body
whereby the heart and lungs are trained to pump blood more efficiently, allowing more oxygen to be delivered to muscles and organs.
What are anaerobic conditions
in the absence of oxygen, preventing normal life for organisms that depend on oxygen
What is the biochemical significance of glycolysis
It is a significant route for carbohydrate metabolism
* It takes place in all the cells of the body
* It is the only pathway that can act in an aerobic and anaerobic environment.
* Skeletal muscles can survive because of anaerobic glycolysis.
* Glycolysis is the only source of energy in erythrocytes.
* The majority of glycolytic pathway reactions are reversible, which is essential for gluconeogenesis or the formation of new glucose.
What is the clinical significance of glycolysis
Pyruvate kinase enzyme deficiency is an autosomal recessive disorder that causes haemolytic anemia.
* Arsenic replaces phosphate in glycolysis steps, which is why arsenic poisoning prevents ATP synthesis.
* Exercise intolerance is caused by muscle Phosphofructokinase deficiency
What are the 2 phases of glycolysis
Energy-requiring (preparatory phase) (steps 1-5)
Energy-releasing (payoff phase) (Steps 6-10)
Where does glycolysis occur
In the cytosol
What is the first step in glycolysis and what is its catalyst
Uptake and Phosphorylation of Glucose
Hexokinases (Mg2+ required)
Describe the uptake and Phosphorylation of glucose stage
- Glucose is phosphorylated to form glucose-6-phosphate.
Hexokinase
* Phosphate group is transferred from ATP to Glucose.
* It is an irreversible step
* Hexokinase has a high affinity for glucose
* Mg2+ is the cofactor in this reaction
* Hexokinase is a key glycolytic enzyme.
* Glucose is phosphorylated to form glucose-6-phosphate.
Glucokinase
* It is present in the liver, where it removes the glucose from the portal vein following a meal.
* Also present in pancreatic cells, where it releases insulin.
* It acts only when blood glucose is more than 100mg/dL.
* Glucokinase has a high affinity for glucose
What is stage 2 of glycolysis and what is the enzyme that catalyses it
Isomerization of Glucose-6-Phsphate to Fructose-6-Phosphate
Phosphoglucoisomerase
Describe the Isomerization of Glucose-6-Phsphate to Fructose-6-Phosphate
Glucose-6-phosphate is isomerized to fructose-6-phosphate by phosphohexose isomerase.
* For the reaction to take place, it needs the help of aldose-ketose isomerization using a catalyst phosphohexose isomerase.
* It causes the glucopyranose ring’s opening to a linear structure changing the structure of the furanose ring of fructose-6-phosphate.
What is step 3 in glycolysis and what is it catalysed by
Phosphorylation of F-6-P to Fructose 1,6-Biphosphate
Phosphofructokinase
Describe the Phosphorylation of F-6-P to Fructose 1,6-Biphosphate
Fructose-6-phosphate is further phosphorylated to fructose 1,6-bisphosphate.
* The enzyme is phosphofructokinase-1. It catalyzes the transfer of a phosphate group from ATP to fructose-6-phosphate.
* It will be the second irreversible step.
* It is a major regulatory step of glycolysis.
* One ATP is utilized in this step.
* Phosphofructokinase-1 is the key enzyme in glycolysis that regulates the breakdown of glucose.
* It is also called the bottleneck or committed step of glycolysis
Why is the Phosphorylation of fructose-6-phosphate important
Prevents re-formation of glucose-6-phosphate
Second phosphate one in each triose in step 4
What is step 4 of glycolysis
Cleavage of Fructose 1,6 Bisphosphate
Aldolase
Describe the Cleavage of Fructose 1,6-Biphosphate
The 6-carbon fructose-1,6-bisphosphate is cleaved into two 3-carbon compounds; one glyceraldehyde-3-phosphate (GAP) and another one is dihydroxyacetone phosphate (DHAP).
* The enzyme which catalyzes the reaction is aldolase. Since the backward reaction is an aldol condensation, the enzyme is called aldolase.
* The reaction is reversible.
What is step 5 of glycolysis and what is it catalysed by
Interconversion of the Triose Phosphates
Triose-phosphate isomerase
Describe the Interconversion of the Triose Phosphates
GAP is on the direct pathway of glycolysis, whereas DHAP is not. Hence Triose-phosphate isomerase converts DHAP into GAP useful for generating ATP. Thus net result is that glucose is now cleaved into 2 molecules of glyceraldehyde-3-phosphate.
* This reaction is rapid and reversible.
Why is the Isomerisation of DHAP to GAP important
Rapid and reversible reaction
Enables us to use both molecules in glycolysis
What is the acronym for Energy-requiring phase of glycolysis
PIPCI
Phosphorylation
Isomerisation
Phosphorylation
Cleavage
Isomerisation
What is step 6 in glycolysis and its catalyst
Oxidative phosphorylation of GAP to 1,3-Bisphosphoglycerate
Glyceraldehyde 3-phosphate dehydrogenase
Lactate Dehydrogenase
Describe Oxidative phosphorylation of GAP to 1,3-Bisphosphoglycerate
The first step in the payoff phase is the oxidation of glyceraldehyde 3-phosphate to a high-energy compound, 1,3-bisphosphoglycerate.
* This reaction is catalyzed by glyceraldehyde 3-phosphate dehydrogenase.
* It is an energy-yielding reaction. During this reaction, NAD+ is reduced and NADH is generated by adding inorganic phosphate.
* This is a reversible reaction.
* Under aerobic conditions, NADH enters into mitochondria.
* Under anaerobic conditions, NADH is utilized by Lactate Dehydrogenase.
Why is the Oxidation and phosphorylation of GAP important
GAP is oxidised, extracting high energy electrons which are picked up by NAD+ to produce NADH
GAP is phosphorylated by the addition of free phosphate
What is step 7 of glycolysis and its catalyst
Conversion of 1,3-Biphosphoglycerate to 3-Phosphoglycerate
1,3-bisphosphoglycerate kinase
Describe the Conversion of 1,3-Biphosphoglycerate to 3-Phosphoglycerate
The enzyme 1,3-bisphosphoglycerate kinase transfers the high-energy phosphoryl group from the carboxyl group of 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate.
* The 1,3-bisphosphoglycerate kinase is the only kinase in glycolysis that is reversible.
* This is a unique example where ATP can be produced at the substrate level without participating in the electron transport chain. This type of reaction where ATP is formed at substrate level is called Substrate level phosphorylation.
Why is substrate-level phosphorylation important
Substrate level phosphorylation of ATP
Near equilibrium reaction
What is stage 8 of glycolysis and its catalyst
Conversion of 3-Phosphoglycerate to 2-Phosphoglycerate
Phosphoglycerate mutase
Describe the Conversion of 3-Phosphoglycerate to 2-Phosphoglycerate
3-phosphoglycerate is isomerized to 2-phosphoglycerate by shifting the phosphate group from 3rd to 2nd carbon atom.
* The enzyme is phosphoglycerate mutase.
* This is a readily reversible reaction.
* Mg2+ is essential for this reaction
What are the important points of the Transfer of phosphate from carbon 3 to carbon 2
Mutases are enzymes that catalyse the transfer of a functional group from one position to another
Phosphate is transferred from position 3 to 2 in preparation for transfer to ADP
What is step 9 of glycolysis and its catalyst
Dehydration of 2-Phosphoglycerate to Phosphoenolpyruvate
Enolase
Describe the Dehydration of 2-Phosphoglycerate to Phosphoenolpyruvate
2-phosphoglycerate is converted to Phosphoenolpyruvate
* The enzyme used is Enolase that requires Mg++.
* The step involves dehydration and one water molecule is removed.
* A high-energy phosphate bond is produced. The reaction is reversible.
What is important about the Enolization step
Dehydration reaction
Forms high-energy phosphoryl compound PEP
What is step 10 in glycolysis and its catalyst
Conversion of Phosphoenol Pyruvate to Pyruvate
Pyruvate Kinase
Describe the Conversion of Phosphoenol Pyruvate to Pyruvate
Phosphoenolpyruvate (PEP) is dephosphorylated to pyruvate, by pyruvate kinase.
* It will be the second substrate-level phosphorylation.
* One mole of ATP is generated during this reaction.
* This step is irreversible
What is important about Step 10 in glycolysis
Substrate level phosphorylation of ATP
Irreversible
What is the acronym for the energy releasing phase
OSTES
Oxidation&Phosphorylation
Substrate level Phos
Transfer
Enolization
Substrate Level Phos
In anaerobic conditions, what is the additional step in glycolysis
When animal tissues cannot be supplied with sufficient oxygen to support aerobic oxidation of the pyruvate and NADH produced in glycolysis, NAD+ is regenerated from NADH by the reduction of pyruvate to lactate.
Some tissues and cell types (such as erythrocytes, which have no mitochondria and thus cannot oxidize pyruvate to CO2) produce lactate from glucose even under aerobic conditions.
The reduction of pyruvate is catalyzed by lactate dehydrogenase.
What are the 3 steps of glycolysis which aren’t reversible
1,3 and 10
